DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice

Abstract

Our previous studies have shown that DJ-1 play important roles in progression of liver diseases through modulating hepatic ROS production and immune response, but its role in hepatic steatosis remains obscure. In the present study, by adopting a high-fat-diet (HFD) induced mice model, we found that DJ-1 knockout (DJ-1-/-) mice showing decreased HFD-induced obesity and visceral adipose accumulation. In line with these changes, there were also reduced liver weight and ameliorated hepatic triglyceride (TG) accumulation in DJ-1-/- mice compared to wild-type (WT) mice. And there were also decreased blood glucose levels and insulin resistance and reduced glucose metabolic disorder in DJ-1-/- mice, whereas there were no significant differences in total cholesterol (TC) and serum lipid in two groups of mice. Mechanistically, we found that there were no differences in food intake in these two genotypes of mice. Furthermore, there were no significant differences in fatty acid synthesis and glycolysis, but the expression of key enzymes in fatty acid oxidation and the tricarboxylic acid (TCA) cycle, such as Cpt1α, Pparα, Acox1, Cs, Idh1 and Idh2, was increased in DJ-1-/- mice liver, suggesting that there was enhanced fatty acids oxidation and TCA cycle in DJ-1-/- mice. Our data indicate that deletion of DJ-1 enhancing fatty acids oxidation resulting in lower hepatic TG accumulation in mice, which protecting mice hepatic steatosis.

Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance

“…6d, f ). Finally, we investigated the effects of Trim28 deletion on the protein DJ-1, which has recently been implicated in the suppression of adipocyte β-oxidation 16 , 17 . We observed a significant ( p < 0.05) increase in Park7 (DJ-1) mRNA expression (Fig.…”

“…We first investigated the protein DJ-1, a mitochondrial protein that has recently been shown inhibit adipocyte fatty acid oxidation 16 , 17 . We demonstrated upregulation of DJ-1 mRNA ( Park7 ) and protein abundance in Trim28 adi-KO mice, and although the exact mechanisms by which DJ-1 participates in lipid metabolism are unknown, increases in DJ-1 in Trim28 adi-KO mice remain consistent with reduced lipolysis and increased lipid storage.…”

Comprehensive analysis of circular RNAs from steatotic livers after ischemia and reperfusion injury by next‐generation RNA sequencing

“…Liver tissue sections were stained with hematoxylin-eosin according to standard procedures. Oil red O (ORO) (O0625; Sigma-Aldrich, St Louis, MO, USA) staining was performed following previously described protocol [17].…”

Comprehensive analysis of circRNAs from steatotic livers after ischemia and reperfusion injury by next generation RNA sequencing

“…Oil red O (ORO) (O0625; Sigma-Aldrich, St Louis, MO) staining were performed following previously described protocol [31].…”